ECE2020 Oral Communications Endocrine-related Cancer (7 abstracts)
Sterol O-Acyl transferase 1 as a prognostic marker of adrenocortical carcinoma
Amanda M Ferreira Lacombe 1 , Ibere Cauduro Soares 2 , João Evangelista Bezerra-Neto 3 , Helaine da Silva Charchar 1 , Ana O Hoff 4 , Madson Q Almeida 1 , Isabel Weigand 5 , Matthias Kroiss 5 , Maria Claudia Nogueira Zerbini 6 & Maria Candida Barisson Villares Fragoso 1
1FMUSP, Unidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM/42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, Sao Paulo, Brazil; 2ICESP, Serviço de Anatomia Patológica, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, Sao Paulo, Brazil; 3ICESP, Serviço de Oncologia Clínica, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, Sao Paulo, Brazil; 4ICESP, Serviço de Endocrinologia, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, Sao Paulo, Brazil; 5Hospital da Universidade de Würzburg, Departamento de Medicina Interna, Unidade de Endocrinologia e Diabetes, Hospital da Universidade de Würzburg, Würzburg, Germany; 6FMUSP, Departamento de Anatomia Patológica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, Sao Paulo, Brazil
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time PCR and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score ≥ 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0–4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort; 37.5% of the ACCs demonstrated strong SOAT1 protein expression (score $ 2), while 62.5% demonstrated weak or absent protein expression (score < 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (P = 0.01), an advanced disease stage [ENSAT 3 and 4 (P = 0.011)] and a high Ki67 index (P = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (HR 2.15, CI 95% 1.26 – 3.66; P = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09 – 4.06; P = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.
Keywords: adrenocortical carcinoma; prognostic factors; SOAT1; target therapies
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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